Enzymes
UniProtKB help_outline | 143 proteins |
GO Molecular Function help_outline |
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Reaction participants Show >> << Hide
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Namehelp_outline
L-arginyl-[protein]
Identifier
RHEA-COMP:10532
Reactive part
help_outline
- Name help_outline L-arginine residue Identifier CHEBI:29965 Charge 1 Formula C6H13N4O SMILEShelp_outline O=C(*)[C@@H](N*)CCCNC(=[NH2+])N 2D coordinates Mol file for the small molecule Search links Involved in 29 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline NAD+ Identifier CHEBI:57540 (Beilstein: 3868403) help_outline Charge -1 Formula C21H26N7O14P2 InChIKeyhelp_outline BAWFJGJZGIEFAR-NNYOXOHSSA-M SMILEShelp_outline NC(=O)c1ccc[n+](c1)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)n2cnc3c(N)ncnc23)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1,186 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Namehelp_outline
ADP-riboxanated L-argininyl-[protein]
Identifier
RHEA-COMP:17719
Reactive part
help_outline
- Name help_outline ADP-2'-imine-ribofurano[1',2':4,5]oxazolidine residue Identifier CHEBI:184300 Charge -2 Formula C21H28N8O14P2 SMILEShelp_outline O(P(OP(=O)(OC[C@H]1O[C@H]([C@@H]([C@@H]1O)O)N2C=NC3=C2N=CN=C3N)[O-])(=O)[O-])C[C@H]4O[C@]5([C@@]([C@@H]4O)(OC(N5CCC[C@@H](C(*)=O)N*)=N)[H])[H] 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,431 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline NH4+ Identifier CHEBI:28938 (CAS: 14798-03-9) help_outline Charge 1 Formula H4N InChIKeyhelp_outline QGZKDVFQNNGYKY-UHFFFAOYSA-O SMILEShelp_outline [H][N+]([H])([H])[H] 2D coordinates Mol file for the small molecule Search links Involved in 528 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline nicotinamide Identifier CHEBI:17154 (Beilstein: 383619; CAS: 98-92-0) help_outline Charge 0 Formula C6H6N2O InChIKeyhelp_outline DFPAKSUCGFBDDF-UHFFFAOYSA-N SMILEShelp_outline NC(=O)c1cccnc1 2D coordinates Mol file for the small molecule Search links Involved in 61 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:69500 | RHEA:69501 | RHEA:69502 | RHEA:69503 | |
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Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
UniProtKB help_outline |
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Gene Ontology help_outline |
Publications
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Shigella evades pyroptosis by arginine ADP-riboxanation of caspase-11.
Li Z., Liu W., Fu J., Cheng S., Xu Y., Wang Z., Liu X., Shi X., Liu Y., Qi X., Liu X., Ding J., Shao F.
Mouse caspase-11 and human caspase-4 and caspase-5 recognize cytosolic lipopolysaccharide (LPS) to induce pyroptosis by cleaving the pore-forming protein GSDMD<sup>1-5</sup>. This non-canonical inflammasome defends against Gram-negative bacteria<sup>6,7</sup>. Shigella flexneri, which causes bacil ... >> More
Mouse caspase-11 and human caspase-4 and caspase-5 recognize cytosolic lipopolysaccharide (LPS) to induce pyroptosis by cleaving the pore-forming protein GSDMD<sup>1-5</sup>. This non-canonical inflammasome defends against Gram-negative bacteria<sup>6,7</sup>. Shigella flexneri, which causes bacillary dysentery, lives freely within the host cytosol where these caspases reside. However, the role of caspase-11-mediated pyroptosis in S. flexneri infection is unknown. Here we show that caspase-11 did not protect mice from S. flexneri infection, in contrast to infection with another cytosolic bacterium, Burkholderia thailandensis<sup>8</sup>. S. flexneri evaded pyroptosis mediated by caspase-11 or caspase 4 (hereafter referred to as caspase-11/4) using a type III secretion system (T3SS) effector, OspC3. OspC3, but not its paralogues OspC1 and 2, covalently modified caspase-11/4; although it used the NAD<sup>+</sup> donor, this modification was not ADP-ribosylation. Biochemical dissections uncovered an ADP-riboxanation modification on Arg314 and Arg310 in caspase-4 and caspase-11, respectively. The enzymatic activity was shared by OspC1 and 2, whose ankyrin-repeat domains, unlike that of OspC3, could not recognize caspase-11/4. ADP-riboxanation of the arginine blocked autoprocessing of caspase-4/11 as well as their recognition and cleavage of GSDMD. ADP-riboxanation of caspase-11 paralysed pyroptosis-mediated defence in Shigella-infected mice and mutation of ospC3 stimulated caspase-11-and GSDMD-dependent anti-Shigella humoral immunity, generating a vaccine-like protective effect. Our study establishes ADP-riboxanation of arginine as a bacterial virulence mechanism that prevents LPS-induced pyroptosis. << Less
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Structural insights into caspase ADPR deacylization catalyzed by a bacterial effector and host calmodulin.
Zhang K., Peng T., Tao X., Tian M., Li Y., Wang Z., Ma S., Hu S., Pan X., Xue J., Luo J., Wu Q., Fu Y., Li S.
Programmed cell death and caspase proteins play a pivotal role in host innate immune response combating pathogen infections. Blocking cell death is employed by many bacterial pathogens as a universal virulence strategy. CopC family type III effectors, including CopC from an environmental pathogen ... >> More
Programmed cell death and caspase proteins play a pivotal role in host innate immune response combating pathogen infections. Blocking cell death is employed by many bacterial pathogens as a universal virulence strategy. CopC family type III effectors, including CopC from an environmental pathogen Chromobacterium violaceum, utilize calmodulin (CaM) as a co-factor to inactivate caspases by arginine ADPR deacylization. However, the molecular basis of the catalytic and substrate/co-factor binding mechanism is unknown. Here, we determine successive cryo-EM structures of CaM-CopC-caspase-3 ternary complex in pre-reaction, transition, and post-reaction states, which elucidate a multistep enzymatic mechanism of CopC-catalyzed ADPR deacylization. Moreover, we capture a snapshot of the detachment of modified caspase-3 from CopC. These structural insights are validated by mutagenesis analyses of CopC-mediated ADPR deacylization in vitro and animal infection in vivo. Our study offers a structural framework for understanding the molecular basis of arginine ADPR deacylization catalyzed by the CopC family. << Less
Mol. Cell 0:0-0(2022) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.
Comments
Multi-step reaction: RHEA:75883 and RHEA:75887